From the Department of Surgery, Division of Plastic Surgery, Yale School of Medicine.
Hansjörg Wyss Department of Plastic Surgery, New York University Langone Health.
Plast Reconstr Surg. 2023 Aug 1;152(2):300e-306e. doi: 10.1097/PRS.0000000000010400. Epub 2023 Mar 14.
Previous work has identified an association between de novo and transmitted loss-of-function mutations in genes under high evolutionary constraint with neurodevelopmental delays in nonsyndromic craniosynostosis (NSC). The authors sought to quantify the neurocognitive effect of these genetic lesions.
In a prospective, double-blinded cohort study, demographic surveys and neurocognitive tests were administered to patients recruited from a national sample of children with sagittal NSC. Scores for academic achievement, Full-Scale Intelligence Quotient (FSIQ), and visuomotor skills were directly compared between patients with and without damaging mutations in genes with a high probability of loss of function intolerance using two-tailed t tests. Analysis of covariance was also used to compare test scores while controlling for surgery type, age at surgery, and sociodemographic risk.
Fifty-six patients completed neurocognitive testing, 18 of whom had a mutation in a highly constrained gene. There was no significant difference between groups in any sociodemographic factors. After controlling for patient factors, patients with high-risk mutations had poorer performance compared with patients without high-risk mutations in every testing category, with significant differences in FSIQ (102.9 ± 11.4 versus 110.1 ± 11.3; P = 0.033) and visuomotor integration (100.0 ± 11.9 versus 105.2 ± 9.5; P = 0.003). There were no significant differences in neurocognitive outcome when stratifying groups based on type of surgery or age at time of surgery.
Even after controlling for exogenous factors, the presence of mutations in high-risk genes led to poorer neurocognitive outcomes. High-risk genotypes may predispose individuals with NSC to deficits, particularly in FSIQ and visuomotor integration.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.
先前的研究已经确定，在非综合征性颅缝早闭（NSC）中，处于高进化约束下的新生和传递的功能丧失突变与神经发育迟缓之间存在关联。作者试图量化这些遗传病变的神经认知效应。
在一项前瞻性、双盲队列研究中，对从全国范围内招募的矢状 NSC 儿童患者进行了人口统计学调查和神经认知测试。使用双侧 t 检验直接比较具有高功能丧失不耐受可能性的基因中存在破坏性突变与不存在破坏性突变的患者的学术成就、全量表智商（FSIQ）和视动技能评分。还使用协方差分析来比较测试分数，同时控制手术类型、手术年龄和社会人口风险因素。
56 名患者完成了神经认知测试，其中 18 名患者的基因发生了高约束基因突变。两组在任何社会人口因素方面均无显著差异。在控制了患者因素后，高风险突变组的患者在每个测试类别中的表现均不如无高风险突变组，FSIQ（102.9 ± 11.4 与 110.1 ± 11.3；P = 0.033）和视动整合（100.0 ± 11.9 与 105.2 ± 9.5；P = 0.003）差异有统计学意义。当根据手术类型或手术时的年龄对患者进行分层时，神经认知结果无显著差异。
即使在控制了外生因素后，高风险基因突变的存在也导致了较差的神经认知结果。高危基因型可能使 NSC 患者易出现缺陷，尤其是在 FSIQ 和视动整合方面。
临床问题/证据水平：风险，II。
